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Self-assessment is essential for health professions education (HPE) students’ lifelong learning as well as future professional practice. A systematic review on self-assessment in HPE was conducted within four electronic databases and resulted in a 43 included articles. Our review found that contextual, teacher-level, and students’ personal attributes contributed to students’ accuracy of self-assessment. In addition, as a pedagogical approach, self-assessment should be implemented together with other instructional activities such as reflection, peer feedback, or video recordings, to have a positive effect on students’ learning outcomes. Our systematic review suggests that we should view self-assessment not only through the lens of assessment, but also as a form of learning activity, and even more importantly, as a learning skill to be developed.